A fungus discovered within the mouse stomach holds the important thing to fungal evolution inside the gut, in response to latest research led by Weill Cornell Medicine investigators. The findings suggest that clinical studies thus far have missed a significant influence of mouse physiology.
Scientists have recently come to understand the importance of microbes — often called “commensals” — that naturally inhabit the gut to human health and disease. For example, bacterial commensals have a significant impact on human immunity. Abnormal changes in these populations have been linked to cancer, inflammatory disorders and even depression. However, how gut fungal commensals influence immunity is less well understood, on account of the dearth of excellent mouse models of fungal commensalism.
The latest study, reported Nov. 27, found that the stomachs of untamed mice contain a yeast called yeast, which is unusually adaptive for mice and advantages them by boosting their immune defenses against parasites. , even though it also increases their risk for some allergies.
“For years we have been looking for a true fungal commensal in mice, but fungal populations in lab mice, as shown by fungal DNA analysis, are transient and vary greatly from colony to colony,” said Dr. Alyan, senior creator of the study. Alioff, an associate professor of immunology in medicine, a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease, and a school member within the Immunology and Microbial Pathogenesis Graduate School Program at Weill Cornell Medicine.
In 2019, a team led by co-author Dr. Barbara Rehrmann of the National Institutes of Health found that “wild” lab mice raised with gut microbes just like those of untamed mice modeled the human immune response compared to standard lab mice. Work higher. Dr. Alev's lab, which participated within the research, found significantly higher levels of fungal DNA in the heart of those mice — levels previously observed in lab mice.
“It was the beginning of a kind of Sherlock Holmes story when we went looking for the dominant fungus, and extended our studies to other rodent populations,” said Dr. Eliff. “And what better place to find wild rats than New York City!”
The team searched for evidence of the fungus in gut samples and other materials provided by pest control corporations in New York City and Los Angeles, and obtained samples from several research institutions that use or sell lab rats. . Eventually, they determined that it was quite common in wild mice, nevertheless it was also often present in lab mouse colonies without researchers knowing about its presence.
“The presence or absence of this fungus should be taken into account in many types of mouse studies,” said co-first creator Dr. Yun Liao, a postdoctoral researcher within the Elio Laboratory.
“The experiment can completely change the results,” said co-first creator Dr. Aris Gao, who was a graduate student within the Elio lab through the study.
The researchers found that it could actually rapidly colonize the gastrointestinal tracts of laboratory mice, is reliably transmitted to newborn mice, and one way or the other evades the antifungal immune system of its hosts, even That it partially inhibits the expansion of other fungal species – all this means that this fungus is evolutionary. It has adapted to living in rodents and is a real commensal.
However, upon fluctuations within the gastrointestinal mucosa brought on by dietary changes or antibiotics, for instance, the fungus appears to the immune system by activating the production of a cytokine called IL-33. This cytokine, in turn, triggers what known as a “type 2” immune response. The team discovered that the fungus advantages its hosts through this enhanced type 2 immune response by symbiotically suppressing other fungi and providing protection against insects, but then again it exacerbates food allergies.
“If you're using mice to research allergies, parasitic infections, cancer development, or any other area where type 2 or type 17 immune responses are relevant, this fungus could be an important factor you need to know. Shouldn't leave.” Elif said.
Although the study suggests that that is model for fungal commensalism, it also raises vital questions: Is this fungus a standard component of the mouse microbiota that ought to at all times be present in lab mice, especially those who touch on immunology? For studies? Is there a fungal commensal that has an analogous role in promoting type 2 immunity in humans?
Dr. Eliff and his lab are actually searching for answers to those questions in samples collected from across the continent in a research collaboration between labs at several institutions, including the Broad Institute, the National Institutes of Health and Penn State. has gone